Enteroviruses (EV) are major human pathogens responsible for a broad spectrum of acute illnesses including meningitis, encephalitis, myocarditis, poliomyelitis, and sepsis. They have also been implicated in chronic diseases such as diabetes mellitus, dermatomyositis, multiple sclerosis and amyotrophic lateral sclerosis. The EV constitute a diverse group of nearly 70 serotypes. Except for the three polioviruses, little is known about their molecular structures or their mechanisms of disease pathogenesis. Furthermore, distinguishing EV infections from those due to bacterial and other viral agents, while critical to the choice of therapy and determination of prognosis, is often impossible on purely clinical grounds. The laboratory diagnosis of EV depends upon growth of virus in tissue culture, an inefficient and sometimes insensitive technology. The diverse antigenic characteristics among the heterogeneous serotypes of EV has hampered their detection by immunoassays. Recently, however, the EV have been shown to share significant portions of their genomic structures, making possible the identification of many EV with one or a few specific nucleic acid probes. The proposed research is to apply such probes to further characterization of the EV and the infections they cause. Specific aims include investigation of the genetic relatedness among the EV, the development and testing of new rapid diagnostic techniques, and elucidation of the pathogenesis of acute and chronic/persistent EV infections. Methodology employed will include solid and liquid phase nucleic acid hybridizations, as well as two in situ hybridization (ISH) techniques performed on a mouse model--classic ISH and whole mouse hybridization. Organs examined will include the central nervous, cardiovascular and gastrointestinal systems, as well as the pregnant mouse and fetus. Specific issues of interest include the tissue tropism, virulence, and persistence of EV. Potential outgrowths of this research include the development of strategies for immunization and therapy of EV infections as well as for their rapid diagnosis.